`
`Author: Christopher Luzzio, MD; Chief Editor: B Mark Keegan, MD, FRCPC more...
`
`Updated: Nov 24, 2014
`Medication Summary
`
`Treatment and management of multiple sclerosis should be targeted toward relieving
`symptoms of the disease, treating acute exacerbations, shortening the duration of an acute
`relapse, reducing frequency of relapses, and preventing disease progression.
`Drugs approved for use in MS that reduce the frequency of exacerbations or slow disability
`progression are referred to as diseasemodifying drugs (DMDs). These DMDs can be further
`classified as immunomodulating (or receptor modulating) or immunosuppressives. Some
`immunosuppressants are also FDAapproved as antineoplastic agents.
`Drugs that treat MSrelated symptoms (eg, acute exacerbations, cognitive dysfunction,
`fatigue, spasticity, bowel and bladder problems, and pain) but do not modify the course of the
`disease are referred to as symptommanagement medications.
`Immunomodulators
`
`Class Summary
`
`Immunomodulators or receptor modulators are indicated for the treatment of patients with
`relapsing forms of MS. They help to slow the accumulation of physical disability and decrease
`the frequency of clinical exacerbations.
`View full drug information
`Interferon beta1b (Betaseron, Extavia)
`
`Interferon beta1b was the first medication approved by the FDA for MS. It is approved for the
`treatment of relapsing forms of MS to reduce the frequency of clinical exacerbations. It has
`shown efficacy in patients who have experienced a first clinical episode and have MRI
`features consistent with MS.[10]
`The exact mechanism by which interferon beta1b exerts its effects is unknown. Interferon
`beta inhibits the expression of proinflammatory cytokines, including interleukin (IL)1 beta,
`tumor necrosis factor (TNF)alpha and TNFbeta, interferon gamma (IFNγ), and IL6. IFNγ
`is believed to be a major factor responsible for triggering the autoimmune reaction leading to
`MS.
`View full drug information
`
`Dalfampridine (Ampyra)
`
`Dalfampridine, a broadspectrum potassium blocker is approved as a treatment to improve
`walking in patients with MS. The improvement in walking was demonstrated by an increase in
`walking speed.[117]
`View full drug information
`Interferon beta1a (Avonex, Rebif)
`
`Interferon beta1a is approved for the treatment of patients with relapsing forms of MS. It
`helps to slow the accumulation of physical disability and decrease the frequency of clinical
`exacerbations.
`The exact mechanism by which interferon beta1a exerts its effects is not fully defined.
`Interferon beta inhibits the expression of proinflammatory cytokines, including interferon
`gamma (IFNγ), which is believed to be a major factor responsible for triggering the
`autoimmune reaction leading to MS.
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`1/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 1
`
`
`
`View full drug information
`
`Alemtuzumab (Lemtrada)
`
`Alemtuzumab is a recombinant monoclonal antibody against CD52 (lymphocyte antigen).
`This action promotes antibodydependent cell lysis. It is indicated for relapsing forms of
`multiple sclerosis. Because of the risk for severe and lasting autoimmune adverse effects,
`use is reserved for patients who have an inadequate response to 2 or more other drugs for
`MS.
`View full drug information
`
`Peginterferon beta1a (Plegridy)
`
`Precise mechanism by which peginterferon beta1a exerts its effects in patients with multiple
`sclerosis is unknown. Interferons are thought to alter response to surface antigen and may
`enhance immune cell activities. It is indicated for treatment of relapsing forms of multiple
`sclerosis.
`View full drug information
`Natalizumab (Tysabri)
`
`Natalizumab is indicated as monotherapy for MS to delay the accumulation of physical
`disability and reduce the frequency of clinical exacerbations. Natalizumab is a recombinant
`humanized monoclonal antibody that binds with alpha4 integrins and inhibits their adherence
`to their counterreceptors. The specific mechanism by which natalizumab exerts its effects in
`MS has not been defined.
`Natalizumab has a blackbox warning for progressive multifocal leukoencephalopathy (PML).
`Because of the risk of PML, natalizumab is available only through a special restricted
`distribution prescribing program called the Tysabri Outreach Unified Commitment to Health
`(TOUCH).
`View full drug information
`
`Glatiramer acetate (Copaxone)
`
`Glatiramer acetate is approved for the reduction of the frequency of relapses in patients with
`relapsingremitting MS, including patients who have experienced a first clinical episode and
`have MRI features consistent with MS. Glatiramer acetate's mechanism of action is unknown,
`but this agent is thought to modify immune processes believed to be responsible for the
`pathogenesis of MS.[12] The recommended dosage is 20 mg/day administered
`subcutaneously. The sites for injection include the arms, abdomen, hips, and thighs.
`View full drug information
`
`Fingolimod (Gilenya)
`
`Fingolimod is the first oral therapy for relapsing forms of MS approved by the FDA. Like other
`diseasemodifying drugs (DMDs) for MS, fingolimod can reduce the frequency of clinical
`exacerbations and delay the accumulation of physical disability. The recommended dosage
`for fingolimod is 0.5 mg once a day.[16]
`The mechanism by which fingolimod exerts therapeutic effects in MS is unknown, but it
`appears to be fundamentally different from that of other MS medications. Its activity may
`involve a reduction of lymphocyte migration into the central nervous system.
`View full drug information
`Teriflunomide (Aubagio)
`
`Teriflunomide is an oral immunomodulatory agent that elicits antiinflammatory effects by
`inhibiting dihydroorotate dehydrogenase, a mitochondrial enzyme involved in pyrimidine
`synthesis. It is indicated for relapsing forms of MS.
`View full drug information
`
`Dimethyl fumarate (Tecfidera)
`
`Dimethyl fumarate (DMF) is an oral Nrf2 pathway activator indicated for relapsing forms of
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`2/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 2
`
`
`
`multiple sclerosis. DMF is metabolized rapidly by presystemic hydrolysis by esterases in the
`GI tract, blood, and tissues (before it reaches systemic circulation) and is converted to its
`active metabolite, monomethyl fumarate (MMF). MMF activates the nuclear factor (erythroid
`derived 2)like 2 (Nrf2) pathway, a transcription factor encoded by the NFE2L2 gene. The
`Nrf2 antioxidant response pathway is a cellular defense against oxidative stress. MMF has
`been identified as a nicotinic acid receptor agonist in vitro.
`Corticosteroids
`
`Class Summary
`
`Corticosteroids are used to reduce inflammation and expedite recovery from acute relapses.
`The most commonly used corticosteroids in MS include methylprednisolone, dexamethasone
`and prednisone. Short courses of intravenous methylprednisolone with or without a short
`prednisone taper have been used.
`View full drug information
`
`Methylprednisolone (SoluMedrol, DepoMedrol
`
`Methylprednisolone is given for acute exacerbations of MS. By reversing increased capillary
`permeability and suppressing polymorphonuclear neutrophil (PMN) activity,
`methylprednisolone may decrease inflammation. In addition, it may alter the expression of
`some proinflammatory cytokines.
`View full drug information
`Dexamethasone (Baycadron, Dexamethasone Intensol)
`
`Dexamethasone can be given for acute exacerbations of MS. It stabilizes cell and lysosomal
`membranes, increases surfactant synthesis, increases serum vitamin A concentration, and
`inhibits prostaglandin and proinflammatory cytokines. Dexamethasone is available as an
`injection that can be administered intravenously or intramuscularly and in various oral
`formulations (tablets, elixir, and solution).
`View full drug information
`
`Prednisone (Sterapred)
`
`Prednisone prevents or suppresses inflammation and immune responses when administered
`at pharmacological doses. Prednisone's actions include inhibition of leukocyte infiltration at
`the site of inflammation, interference in the function of mediators of inflammatory response,
`and suppression of humoral immune responses. Oral prednisone tapers are commonly
`administered with or without methylprednisolone.
`Immunosuppressants
`
`Class Summary
`
`Immunosuppressants are used for their ability to suppress immune reactions. Agents such as
`methotrexate have shown some effectiveness in delaying progression of impairment of the
`upper extremities in patients with secondary progressive MS. Azathioprine has been studied
`in clinical trials and has shown modest effects on relapses and progression of disease.
`Methotrexate and azathioprine have not been approved by the US Food and Drug
`Administration for use in MS.
`View full drug information
`Azathioprine (Azasan, Imuran)
`
`This immunosuppressive antimetabolite drug is an imidazolyl derivative of 6mercaptopurine.
`It is cleaved in vivo to mercaptopurine and converted to 6thiouric acid by xanthine oxidase.
`Azathioprine is generally used in the treatment of transplant rejection or severe, active,
`erosive rheumatoid arthritis, but it has been used offlabel for MS.[128]
`View full drug information
`
`Methotrexate (Rheumatrex)
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`3/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 3
`
`
`
`Methotrexate interferes with DNA synthesis, repair, and cellular replication. It inhibits
`dihydrofolic acid reductase, which participates in the synthesis of thymidylate and purine
`nucleotides. Methotrexate has been used offlabel for MS.
`Antineoplastic Agents
`
`Class Summary
`
`Antineoplastic agents such as cyclophosphamide and mitoxantrone have been used in MS
`patients.
`View full drug information
`
`Mitoxantrone
`
`Mitoxantrone is an immunosuppressive agent approved for the treatment of secondary
`progressive or aggressive relapsingremitting MS. It is used for reducing neurologic disability
`and/or the frequency of clinical relapses in patients with secondary (longterm) progressive,
`progressive relapsing, or worsening relapsingremitting MS (ie, patients whose neurologic
`status is significantly abnormal between relapses). Mitoxantrone is not indicated in the
`treatment of patients with primary progressive MS.
`Mitoxantrone therapy can increase the risk of developing secondary acute myeloid leukemia
`(AML) in MS patients and in patients with cancer.[15]
`View full drug information
`Cyclophosphamide
`
`Cyclophosphamide has been used for the treatment of progressive MS. Evidence of benefit
`is mixed. This agent has not been approved for MS but has been used offlabel in MS
`patients. Cyclophosphamide is associated with leukemia, lymphoma, infection, and
`hemorrhagic cystitis.[129]
`Dopamine Agonists
`
`Class Summary
`
`Amantadine is approved for the prophylaxis and treatment of influenza A and Parkinson
`disease and has been used offlabel to relieve fatigue in patients with MS. It has relatively
`few side effects and is well tolerated .
`View full drug information
`
`Amantadine (Symmetrel)
`
`Amantadine is not FDA approved for use in MS, but dosages of 100 mg given orally twice a
`day have commonly been used for fatigue.[114] The mechanism by which amantadine
`counteracts fatigue in MS patients is unclear.
`Skeletal Muscle Relaxant
`
`Class Summary
`
`Pharmacologic treatment of spasticity includes baclofen (Lioresal, Gablofen) as a firstline
`agent. Baclofen can be titrated easily in divided doses. Patients using this medication may
`report fatigue or weakness as an adverse effect. Dantrolene (Dantrium) acts within muscles
`on excitationcontraction coupling; however, it is rarely used because it can cause liver
`damage.
`View full drug information
`
`Baclofen (Lioresal, Gablofen)
`
`Baclofen is a skeletal muscle relaxant used as a firstline treatment for spasticity in patients
`with MS. It can effectively relieve spasms and has modest effects in improving performance.
`Intrathecal baclofen via an implanted pump can be effective against spasticity in suitable
`patients. The pump can be electronically regulated to deliver small amounts of baclofen at a
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`4/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 4
`
`
`
`constant or variable dose over a 24hour period to increase efficacy and decrease side
`effects.
`View full drug information
`
`Dantrolene (Dantrium)
`
`Dantrolene is a skeletal muscle relaxant that acts directly on skeletal muscle to decrease
`spasticity. Dantrolene is believed to decrease muscle contraction by directly interfering with
`calcium ion release from the sarcoplasmic reticulum within skeletal muscle cells. It affects all
`muscles of the body and is used less frequently than baclofen because of hepatotoxicity at
`higher doses and numerous drug interactions.
`Neuromuscular Blockers, Botulinum Toxins
`
`Class Summary
`
`The FDA has approved the use of botulinum toxin (Botox) for the treatment of upper limb
`spasticity in MS. The FDA has also approved this agent for the treatment of urinary
`incontinence due to detrusor overactivity associated with a neurologic condition (eg, MS) in
`adults who have an inadequate response to, or are intolerant of, an anticholinergic
`medication.
`View full drug information
`OnabotulinumtoxinA toxin (Botox)
`
`OnabotulinumtoxinA toxin is an injectable neurotoxin that temporarily blocks connections
`between the nerves and the muscles, leading to shortterm relaxation of the targeted muscle.
`The drug can be injected again when the musclerelaxing effects have worn off, but not more
`frequently than every 3 months.
`It is approved for the treatment of upper limb spasticity in adults to decrease the severity of
`increased muscle tone in elbow flexors (biceps), wrist flexors (flexor carpi radialis and flexor
`carpi ulnaris), and finger flexors (flexor digitorum profundus and flexor digitorum sublimis).
`Alpha2Adrenergic Agonists
`
`Class Summary
`
`Tizanidine (Zanaflex) is a centrally active alpha2 adrenergic agonist that is also used to treat
`spasticity in patients with MS. It can be used alone or in combination with baclofen.
`View full drug information
`
`Tizanidine (Zanaflex)
`
`This centrally acting alphaadrenergic agonist is presumed to decrease spasticity by
`increasing presynaptic inhibition of motor neurons. Tizanidine has effects similar to those of
`baclofen, but it produces less weakness and more sedation. This drug can be titrated starting
`with 2 mg, with maximum doses of 36 mg/day.
`Benzodiazepines
`
`Class Summary
`
`Benzodiazepines are used as secondline agents for the treatment of spasticity in patients
`with MS. Agents in the benzodiazepine class that are commonly used include diazepam and
`clonazepam. While these compounds can be useful adjunct medications, they can be
`sedating and habitforming and are not FDA approved for use in MS.
`For patients who also experience sleep disorders, the provider may take advantage of the
`sedating effects of the benzodiazepines to manage the spasticity and sleep problem with a
`single medication. For patients with cognitive impairment, benzodiazepines may be
`contraindicated due to their adverse CNS effects.
`View full drug information
`
`Clonazepam (Klonopin)
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`5/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 5
`
`
`
`Clonazepam is a longacting benzodiazepine that increases presynaptic gamma
`aminobutyric acid (GABA) inhibition and reduces monosynaptic and polysynaptic reflexes. It
`suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other
`inhibitory transmitters.
`View full drug information
`
`Diazepam (Valium)
`
`Diazepam modulates the postsynaptic effects of GABAA transmission, resulting in an
`increase in presynaptic inhibition. It appears to act on part of the limbic system, the thalamus,
`and the hypothalamus to induce a calming effect. Diazepam also has been found to be an
`effective adjunct for the relief of skeletal muscle spasms caused by upper motor neuron
`disorders.
`Stimulants
`
`Class Summary
`
`Modafinil (Provigil), armodafinil (Nuvigil), dextroamphetamine (Dexedrine), and
`methylphenidate (Concerta, Metadate CD, Metadate ER, Ritalin, Ritalin SR) are wakefulness
`promoting agents approved for the treatment of narcolepsy. These agents are also used for
`the treatment of fatigue without interfering with normal sleep architecture in patients with MS.
`Modafinil and methylphenidate have also been used as cognitiveenhancing drugs to treat
`cognitive dysfunction in MS.
`View full drug information
`Modafinil (Provigil)
`
`Modafinil is listed in Schedule IV of the Controlled Substances Act. It promotes wakefulness,
`and is used for treatment of fatigue without interfering with normal sleep architecture.
`Patients should be observed for signs of use or abuse, as the drug has psychoactive and
`euphoric effects similar to those seen with other scheduled CNS stimulants (eg,
`methylphenidate). The mechanism of action of modafinil is unknown.
`View full drug information
`
`Armodafinil (Nuvigil)
`
`Armodafinil elicits wakefulnesspromoting actions similar to those of sympathomimetic
`agents, although its pharmacologic profile is not identical to sympathomimetic amines. It is
`indicated to improve wakefulness in individuals with excessive sleepiness associated with
`narcolepsy, obstructive sleep apnea–hypopnea syndrome (OSAHS), or shiftwork sleep
`disorder. It is also used for treatment of fatigue without interfering with normal sleep
`architecture. It may also be used as a cognitiveenhancing drug to treat cognitive dysfunction
`in MS.
`View full drug information
`
`Methylphenidate (Concerta, Daytrana, Metadate CD, Metadate ER,
`Methylin, Methylin ER, Ritalin, Ritalin LA, Ritalin SR)
`
`Methylphenidate is a piperidine derivative. It stimulates the cerebral cortex and subcortical
`structures.
`View full drug information
`Dextroamphetamine (Dexedrine, ProCentra)
`
`This agent increases the amount of circulating dopamine and norepinephrine in the cerebral
`cortex by blocking the reuptake of norepinephrine or dopamine from synapses.
`Anticonvulsants, Other
`
`Class Summary
`
`Gabapentin is an anticonvulsant drug that is particularly useful in patients who experience
`spasticity and neuropathic pain. Anticonvulsants (eg, carbamazepine, phenytoin) can also be
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`6/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 6
`
`
`
`used for the treatment of secondary pain in MS. Topiramate (Topamax) is an anticonvulsant
`that can be used for MS patients with tremor or spasms and has also been used for
`paroxysmal symptoms.
`View full drug information
`
`Gabapentin (Neurontin)
`
`Gabapentin is a membrane stabilizer, a structural analogue of the inhibitory neurotransmitter
`GABA. Paradoxically, gabapentin is thought not to exert an effect on GABA receptors. It is
`used to manage pain and provide sedation in patients with neuropathic pain.
`View full drug information
`
`Carbamazepine (Tegretol, Tegretol XR)
`
`Carbamazepine is a sodium channel blocker that typically provides substantial or complete
`relief of pain in 80% of individuals with MS within 2448 hours. It reduces sustained high
`frequency repetitive neural firing and is a potent enzyme inducer that can induce its own
`metabolism.
`View full drug information
`Pregabalin (Lyrica)
`
`Pregabalin is a structural derivative of GABA with an unknown mechanism of action. It is
`used to relieve neuropathic pain.
`View full drug information
`
`Topiramate (Topamax)
`
`The exact mechanism of topiramate's anticonvulsant effects is unknown. Topiramate's
`actions involve several mechanisms, including reduction of the duration of abnormal
`discharges and the number of action potentials within each discharge. This is probably
`secondary to its ability to block voltagesensitive sodium channels. Topiramate also increases
`the frequency at which GABA activates GABAA receptors. Finally, it inhibits excitatory
`transmission by antagonizing some types of glutamate receptors.
`Anticonvulsants, Hydantoins
`
`Class Summary
`
`Anticonvulsants, such as phenytoin, can also be used for the treatment of secondary pain in
`MS.
`View full drug information
`Phenytoin (Dilantin, Phenytek)
`
`Phenytoin blocks sodium channels nonspecifically and therefore reduces neuronal excitability
`in sensitized Cnociceptors. It is effective in neuropathic pain, but it suppresses insulin
`secretion and may precipitate hyperosmolar coma in patients with diabetes.
`Selective Serotonin/Norepinephrine Reuptake Inhibitors
`
`Class Summary
`
`Selective serotonin/norepinephrine reuptake inhibitors (SNRIs) are principally used as
`antidepressants; however, duloxetine is also indicated for relief of several types of pain.
`View full drug information
`Duloxetine (Cymbalta)
`
`A potent inhibitor of neuronal serotonin and norepinephrine uptake, duloxetine is used as an
`antidepressant and for relief of neuropathic pain.
`Nonsteroidal AntiInflammatory Drugs
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`7/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 7
`
`
`
`Class Summary
`
`Pharmacologic agents used for the treatment of secondary pain in MS are nonsteroidal anti
`inflammatory drugs (NSAIDs) or other analgesics. Ibuprofen has also been cited as
`potentially having beneficial effects with paroxysmal symptoms. The use of narcotics seldom
`is indicated. Commonly used NSAIDs include ibuprofen (Motrin, Advil) and naproxen
`(Naprosyn, Aleve, Anaprox, Anaprox DS, Naprelan).
`View full drug information
`Ibuprofen (Motrin, Advil)
`
`Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory
`reactions and pain by decreasing prostaglandin synthesis.
`View full drug information
`
`Naproxen (Naprosyn, Aleve, Anaprox, Anaprox DS, Naprelan)
`
`Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and
`pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin
`synthesis.
`Antispasmodic Agents, Urinary
`
`Class Summary
`
`Treatment of bladder dysfunction in MS patients includes suppressing urgency and ensuring
`effective urinary drainage. Antispasmodic agents that help decrease muscle spasms of the
`bladder and the frequent urge to urinate caused by spasms include oxybutynin (Ditropan,
`Ditropan XL) or tolterodine (Detrol, Detrol LA).
`View full drug information
`Tolterodine (Detrol, Detrol LA)
`
`Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction
`and salivation are mediated via cholinergic muscarinic receptors.
`View full drug information
`
`Oxybutynin (Ditropan, Ditropan XL)
`
`Oxybutynin is an antispasmodic that exerts a direct effect on smooth muscle and inhibits the
`muscarinic effects of acetylcholine on smooth muscle. This results in relaxation of bladder
`smooth muscle. It is indicated for the relief of urinary symptoms in patients with uninhibited
`and reflex neurogenic bladder. It is metabolized by the liver and excreted renally.
`Acetylcholinesterase Inhibitors, Central
`
`Class Summary
`
`Multiple sclerosis may affect cognition, and cognitionenhancing drugs have been met with
`some success in MS patients. Treatments used in Alzheimer disease, such as donepezil
`(Aricept), may have some potential beneficial effects; however, it has not been proven in
`clinical trials. Donepezil is not FDAapproved for use in MS. Depression may also contribute
`to cognitive dysfunction and should be treated if it is diagnosed.
`View full drug information
`
`Donepezil (Aricept)
`
`Donepezil selectively inhibits acetylcholinesterase, the enzyme responsible for the
`destruction of acetylcholine, and improves the availability of acetylcholine.
`Laxatives
`
`Class Summary
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`8/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 8
`
`
`
`Pharmacologic management of constipation in patients with MS includes the use of stool
`softeners. Stool softeners, such as docusate sodium (Colace), work by decreasing surface
`tension, allowing water to enter the stool.
`View full drug information
`
`Docusate sodium (Colace, DSS, Philips LiquiGels, Silace, Soflax)
`
`Docusate sodium allows the incorporation of water and fat into stools, causing stools to
`soften. By its surface active properties, docusate sodium keeps stools soft for easy, natural
`passage. Docusate sodium is not a laxative and, thus, is not habitforming. Tachyphylaxis
`may occur with longterm use. This agent is effective acutely and does not induce defecation.
`View full drug information
`
`Psyllium (Fiberall, Konsyl, Metamucil)
`
`Psyllium is administered orally and absorbs liquid in the GI tract, thereby altering intestinal
`fluid and electrolyte transport. Absorption of liquid also causes expansion of the stool, and
`the resultant bulk facilitates peristalsis and bowel motility.
`View full drug information
`Methylcellulose (Citrucel)
`
`Methylcellulose increases the bulk of the stool and thereby stimulates peristalsis, which
`increases bowel motility and decreases GI transit time. These actions of methylcellulose
`result in easy passage of stool in patients with chronic constipation.
`Antidiarrheals
`
`Class Summary
`
`Diarrhea, if it occurs, typically is not related to MS per se; it is more likely due to fecal
`impaction, diet, irritation of the bowel, or overuse of laxatives or stool softeners, or it is an
`adverse effect of medications. Diphenoxylate and atropine (Lomotil) is an antidiarrheal that
`helps slow the muscles of the bowel.
`View full drug information
`
`Diphenoxylate and atropine (Lomotil)
`
`Diphenoxylate appears to exert its effect locally and centrally on the smooth muscle cells of
`the GI tract to inhibit GI motility and slow excess GI propulsion. A subtherapeutic dose of
`anticholinergic atropine sulfate is added to discourage overdosage, in which case
`diphenoxylate may clinically mimic the effects of codeine.
`
`Contributor Information and Disclosures
`Author
`Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology,
`University of Wisconsin at Madison School of Medicine and Public Health
`
`Christopher Luzzio, MD is a member of the following medical societies: American Academy
`of Neurology
`
`Disclosure: Nothing to disclose.
`Coauthor(s)
`Fernando Dangond, MD, FAAN Head of US Medical Affairs, Neurodegenerative
`Diseases, EMD Serono, Inc.
`
`Fernando Dangond, MD, FAAN is a member of the following medical societies: American
`Academy of Neurology and American Medical Association
`
`Disclosure: EMD Serono, Inc. Salary Employment
`Chief Editor
`B Mark Keegan, MD, FRCPC Associate Professor of Neurology, College of Medicine,
`Mayo Clinic; Master's Faculty, Mayo Graduate School; Consultant, Department of
`Neurology, Mayo Clinic, Rochester
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`9/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 9
`
`
`
`B Mark Keegan, MD, FRCPC is a member of the following medical societies: American
`Academy of Neurology, American Medical Association, and Minnesota Medical Association
`
`Disclosure: Nothing to disclose.
`Additional Contributors
`Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University
`School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine,
`Wake Forest Baptist Medical Center
`Martin K Childers, DO, PhD is a member of the following medical societies: American
`Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation
`Medicine, American Osteopathic Association, Christian Medical & Dental Society, and
`Federation of American Societies for Experimental Biology
`Disclosure: Allergan pharma Consulting fee Consulting
`Edmond A Hooker II, MD, DrPH, FAAEM Assistant Professor, Department of Emergency
`Medicine, University of Cincinnati College of Medicine
`Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies:
`American Academy of Emergency Medicine, American Public Health Association, Society
`for Academic Emergency Medicine, and Southern Medical Association
`Disclosure: Nothing to disclose.
`J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology,
`Department of Emergency Medicine, University of Virginia School of Medicine
`J Stephen Huff, MD is a member of the following medical societies: American Academy of
`Emergency Medicine, American Academy of Neurology, American College of Emergency
`Physicians, and Society for Academic Emergency Medicine
`Disclosure: Nothing to disclose.
`Marjorie Lazoff, MD EditorinChief, Medical Computing Review
`Marjorie Lazoff, MD is a member of the following medical societies: Alpha Omega Alpha,
`American College of Emergency Physicians, American Medical Informatics Association,
`and Society for Academic Emergency Medicine
`Disclosure: Nothing to disclose.
`Consuelo T Lorenzo, MD Physiatrist, Department of Physical Medicine and Rehabilitation,
`Alegent Health, Immanuel Rehabilitation Center
`Consuelo T Lorenzo, MD is a member of the following medical societies: American
`Academy of Physical Medicine and Rehabilitation
`Disclosure: Nothing to disclose.
`William J Nowack, MD Associate Professor, Epilepsy Center, Department of Neurology,
`University of Kansas Medical Center
`William J Nowack, MD is a member of the following medical societies: American Academy
`of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society,
`American Medical Electroencephalographic Association, American Medical Informatics
`Association, and Biomedical Engineering Society
`Disclosure: Nothing to disclose.
`Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of
`Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine
`Richard Salcido, MD is a member of the following medical societies: American Academy of
`Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American
`College of Physician Executives, American Medical Association, and American Paraplegia
`Society
`Disclosure: Nothing to disclose.
`Daniel D Scott, MD, MA Associate Professor, Department of Physical Medicine and
`Rehabilitation, University of Colorado School of Medicine; Attending Physician, Department
`of Physical Medicine and Rehabilitation, Denver Veterans Affairs Medical Center, Eastern
`Colorado Health Care System
`Daniel D Scott, MD, MA is a member of the following medical societies: Alpha Omega
`Alpha, American Academy of Physical Medicine and Rehabilitation, American Association
`of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society,
`
`5/28/2015
`
`Multiple Sclerosis Medication
`
`http://emedicine.medscape.com/article/1146199-medication#1
`
`10/18
`
`MYLAN PHARMS. INC. EXHIBIT 1118 PAGE 10
`
`
`
`Association of Academic Physiatrists, National Multiple Sclerosis Society, and Physiatric
`Association of Spine, Sports and Occupational Rehabilitation
`Disclosure: Nothing to disclose.
`FuDong Shi, MD, PhD Director of Neuroimmunology Laboratory, Barrow Neurological
`Institute, St Joseph's Hospital and Medical Center
`Disclosure: Nothing to disclose.
`Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska
`Medical Center College of Pharmacy; EditorinChief, Medscape Drug Reference
`Disclosure: Medscape Salary Employment
`Florian P Thomas, MD, MA, PhD, Drmed Director, Spinal Cord Injury Unit, St Louis
`Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center;
`Director, Neuropathy Association Center of Excellence, Professor, Department of
`Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and
`Department of Molecular Microbiology and Immunology, St Louis University School of
`Medicine
`Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies:
`American Academy of Neurology, American Neurological Association, American
`Paraplegia Society, Consortium of Multiple Sclerosis Centers, and National Multiple
`Sclerosis Society
`Disclosure: Nothing to disclose.
`Timothy Vollmer, MD Consulting Staff, Department of Emergency Medicine, Geisinger
`Medical Center
`Disclosure: Nothing to disclose.
`Sandra F Williamson, MS, ANPC, CRRN Clinic Coordinator, Department of
`Rehabilitation Medicine, Denver Veterans Affairs Medical Center
`Sandra F Williamson, MS, ANPC, CRRN is a member of the following medical societies:
`Phi Beta Kappa, Phi Kappa Phi, and Sigma Theta Tau International
`Disclosure: Nothing to disclose.
`
`References
`
`1. Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al.
`Alemtuzumab ve